Experimental Models for Assaying Microvascular Endothelial Cell Pathophysiology in Stroke

Camós, Susanna; Mallolas, Judith

doi:10.3390/molecules15129104

Cited by 31 publications

(22 citation statements)

References 130 publications

(233 reference statements)

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“…in cell differentiation, self‐polymerizing ECM models (cross‐linked ECM) can only provide a uniform matrix lacking the discontinuities and gaps that may normally be present in vivo and allow for cell migration. This problem was partially addressed by using cell‐derived matrices, which maintain some of the original gaps that accommodate the cells 164,166. The omission of minor ECM constituents potentially significant in the architectural assembly and matrix property is another concern until more sophisticated 3D matrix models become available in the future.…”

Section: Dynamic In Vitro Bbb Modelsmentioning

confidence: 99%

In Vitro Blood–Brain Barrier Models: Current and Perspective Technologies

Naik

Cucullo

2012

Journal of Pharmaceutical Sciences

245

188

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Even in the 21st century, studies aimed at characterizing the pathological paradigms associated with the development and progression of central nervous system diseases are primarily performed in laboratory animals. However, limited translational significance, high cost, and labor to develop the appropriate model (e.g., transgenic or inbred strains) have favored parallel in vitro approaches. In vitro models are of particular interest for cerebrovascular studies of the blood–brain barrier (BBB), which plays a critical role in maintaining the brain homeostasis and neuronal functions. Because the BBB dynamically responds to many events associated with rheological and systemic impairments (e.g., hypoperfusion), including the exposure of potentially harmful xenobiotics, the development of more sophisticated artificial systems capable of replicating the vascular properties of the brain microcapillaries are becoming a major focus in basic, translational, and pharmaceutical research. In vitro BBB models are valuable and easy to use supporting tools that can precede and complement animal and human studies. In this article, we provide a detailed review and analysis of currently available in vitro BBB models ranging from static culture systems to the most advanced flow-based and three-dimensional coculture apparatus. We also discuss recent and perspective developments in this ever expanding research field.

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Section: Dynamic In Vitro Bbb Modelsmentioning

confidence: 99%

In Vitro Blood–Brain Barrier Models: Current and Perspective Technologies

Naik

Cucullo

2012

Journal of Pharmaceutical Sciences

245

188

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“…A number of in vitro models using cerebral microvascular endothelial cells have been employed to study the effects of ischaemia and reperfusion on the BBB, and to test novel therapeutics. Specifically, the majority of these studies have employed the oxygen glucose deprivation (OGD) method, with or without reoxygenation (RO), using primary or immortalised cerebral microvascular endothelial cells from a number of different species including humans, rats, mice and pigs . Primary cerebral capillary endothelial cells have the closest similarity to the BBB phenotype in vivo at low passage numbers .…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, the majority of these studies have employed the oxygen glucose deprivation (OGD) method, with or without reoxygenation (RO), using primary or immortalised cerebral microvascular endothelial cells from a number of different species including humans, rats, mice and pigs . Primary cerebral capillary endothelial cells have the closest similarity to the BBB phenotype in vivo at low passage numbers . However, primary cells are difficult to extract, can often be contaminated with other cell types of the neurovascular unit (i.e.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of a mouse cerebral microvascular endothelial cell line (bEnd.3) after oxygen glucose deprivation and reoxygenation

Taher

Chin

et al. 2016

Clin Exp Pharma Physio

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Studies have utilised immortalised mouse cerebral endothelial cells (bEnd.3) exposed to oxygen glucose deprivation (OGD) to study blood-brain barrier (BBB) disruption after ischaemia. However, there is a paucity of literature describing the duration of OGD (and reoxygenation [RO]) required to best simulate BBB disruption in vivo. In this study we assessed BBB disruption in bEnd.3 cells after exposure to a range of OGD periods, and also after OGD + RO. Exposure of bEnd.3 monolayers to 4, 6, 16, or 24 hours of OGD resulted in a significant increase in permeability. The hyperpermeability after 16 or 24 hours was associated with decreased expression of tight junction proteins (occludin and claudin-5). Furthermore, there was a decrease in cell viability and increased expression of the pro-apoptotic protein, cleaved caspase-3. Exposure of bEnd.3 monolayers to 1 hour OGD+ 23 hours RO exacerbated hyperpermeability relative to 1 hour OGD, which was associated with decreased expression levels of occludin and ZO-1, but no change in cell viability or caspase-3. 4 hours OGD + 23 hours RO exacerbated hyperpermeability, decreased expression levels of tight junction proteins, decreased cell viability, and increased caspase-3 expression. Thus, bEnd.3 cells exhibit hyperpermeability, a loss of tight junction proteins, and undergo cell death, after exposure to prolonged periods of OGD. Moreover, they exhibit exacerbated hyperpermeability, a loss of tight junction proteins, and increased expression of caspase-3 after OGD + RO. These findings will facilitate the use of this cell line in studies of BBB disruption and for the testing of therapeutics.

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“…[67] We should understand the molecular mechanisms of neuronal death following stroke in order to foster drug discovery and screening. [68] In one recent example, Samson et al replicated the spreading neurotoxicity following cerebral ischemia and traumatic brain injury using hippocampal neurons cultured in a microfluidic platform. [69] The neurons were environmentally isolated but synaptically connected – to assess neuroprotection and overcome the challenge in animal models of separating initial brain lesion from the entire brain response.…”

Section: Recapitulating the Human Brain Pathophysiologymentioning

confidence: 99%

Three‐Dimensional Models of the Human Brain Development and Diseases

Jorfi

D’Avanzo

Kim

et al. 2017

Adv Healthcare Materials

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Deciphering the human brain pathophysiology remains one of the greatest challenges of the 21st century. Neurological disorders represent a significant proportion of diseases burden; however, the complexity of the brain physiology makes it challenging to model its diseases. Simple in vitro models have been very useful for precise measurements in controled conditions. However, existing models are limited in their ability to replicate complex interactions between various cells in the brain. Studying human brain requires sophisticated models to reconstitute the tangled architecture and functions of brain cells. Recently, advances in the development of three-dimensional (3D) brain cell culture models have begun to recapitulate various aspects of the human brain physiology in vitro and replicate basic disease processes of Alzheimer’s disease, amyotrophic lateral sclerosis, and microcephaly. In this review, we discuss the progress, advantages, limitations, and future directions of 3D cell culture systems for modeling the human brain development and diseases.

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Experimental Models for Assaying Microvascular Endothelial Cell Pathophysiology in Stroke

Cited by 31 publications

References 130 publications

In Vitro Blood–Brain Barrier Models: Current and Perspective Technologies

In Vitro Blood–Brain Barrier Models: Current and Perspective Technologies

Characterisation of a mouse cerebral microvascular endothelial cell line (bEnd.3) after oxygen glucose deprivation and reoxygenation

Three‐Dimensional Models of the Human Brain Development and Diseases

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